Receptors that bind specific molecules (e.g., a hormone, drug, cytokine, or biochemical) have been identified on a multitude of cell types. Receptors are found on the cell surface or, in the case of soluble receptors, are released into the serum. Effort has been directed toward isolation and characterization of a number of receptors in order to study their physiological roles and to explore possible therapeutic uses. The binding of a particular target molecule by a soluble receptor administered to a patient may alleviate disorders mediated by the target molecule.
Certain receptors have been found to comprise two separate polypeptide chains associated in the form of a complex. Such two-chain receptors often bind the target molecule with greater affinity than that exhibited by one of the chains alone.
Leukemia inhibitory factor (LIF) is a polypeptide hormone that plays a central role in the regulation of diverse adult and embryonic systems. LIF acts on a variety of cell types and has multiple biological activities. The diversity in biological activity is reflected in the various synonyms of LIF, which include hepatocyte stimulating factor III (Baumann and Wong, J. Immunol. 143:1163 [1989]); cholinergic nerve differentiation factor (Yamamori et al., Science 246:1412 [1990]); melanoma-derived lipoprotein lipase inhibitor (Mori et al., Biochem. Biophys. Res. Comm. 160:1085 [1989]); human interleukin for DA cells (Moreau et al., Nature 336:690 [1988]); differentiation factor (Tomida et al., J. Biol. Chem. 259:10978 [1984]); differentiation inhibitory factor (Abe et al., J. Biol. Chem. 264; 8941 [1989]); differentiation inhibitory activity (Smith and Hooper, Devel. Biol;. 121:1 [1987]); and differentiation retarding factor (Koopman and Cotton, Exp. Cell. Res. 154:233 [1984].
The cloning of a leukemia inhibitory factor receptor (LIF-R) has been reported by Gearing et al. in EMBO J. 10:2839 (1991). This recombinant single-chain LIF-R polypeptide binds LIF, but with lower affinity than the naturally occurring LIF receptors found on certain normal cells. A receptor that binds LIF with higher affinity than that exhibited by this cloned single chain LIF-R would be desirable for certain applications.
Oncostatin M is a secreted single-chain polypeptide cytokine that regulates the growth of certain tumor-derived and normal cell lines. Oncostatin M is produced by activated lymphoid cells. A number of cell types have been found to bind the oncostatin M protein. See, for example, Linsley et al., J. Biol. Chem., 264:4282 (1989). However, the isolation and characterization of an oncostatin M receptor have not been reported.